Browsing by Author "Gaspar, Marcos A."
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- Contribution of HFE and HPSE genes and methaemoglobin reductase activity to heart failurePublication . Gaspar, Marcos A.; Aguiar, Laura; Ferreira, Joana; Faustino, Paula; Mascarenhas, Mário Rui; Menezes Falcão, Luiz; Bicho, Manuel; Inácio, ÂngelaIntroduction: Heart failure can be defined as a syndrome caused by a structural anomaly and/or by a committed cardiac function, which leads to an inadequate cardiac output unable to meet the metabolic necessities of the organism. We aim to understand if HFE and HPSE genes as well as methaemoglobin reductase activity, may influence the development of heart failure. Methodology: It was performed a case-control study, in which 252 DNA samples from Portuguese individuals were analysed, 143 derived from subjects with heart failure, and 109 from healthy controls. For HPSE genotyping (rs4693608), we performed endpoint PCR analysis. A multiplex ARMS (Amplification-Refractory Mutation System) assay was used for the simultaneous detection of two HFE polymorphisms (C282Y and H63D). Reductase methaemoglobin activity was determined by spectrophotometric methods. All statistical tests were performed with IBM® SPSS® Statistics 26.0 software. Statistical significance was defined as a p-value < 0.05. Results: Regarding the H63D polymorphism, results show the CG genotype as a risk factor [OR (95% CI) = 2.889 (1.041-8.018); p=0.042]. In what concerns HPSE gene, the GG genotype was found to have a protective effect [OR (95% CI) = 0.435 (0.193-0.982); p=0.045] while the presence of the A allele is a risk factor [OR (95% CI) = 2.297 (1.018-5.179); p=0.045. Considering methaemoglobin reductase, its activity was lower in patients than in healthy controls (p=0.019). Discussion: Intravenous iron supplementation is sometimes considered in heart failure treatment, emphasizing the results presented in the present study. Considering the high prevalence of heart failure in Portugal (400.000 individuals, according to Sociedade Portuguesa de Cardiologia), it is important to identify iron-related markers, since it may allow an earlier and more expert approach, which may provide better prevention and therapeutic strategies for this pathology.
- Estudo da interação entre moduladores da homeostasia do ferro e o gene ECA na insuficiência cardíacaPublication . Gaspar, Marcos A.; Aguiar, Laura; Ferreira, Joana; Faustino, Paula; Mascarenhas, Mário Rui; Menezes Falcão, Luís; Bicho, Manuel; Inácio, ÂngelaIntrodução: A insuficiência cardíaca (IC) diz respeito a um síndrome clínico composto por um conjunto de sintomas e/ou sinais com origem numa anomalia cardíaca estrutural e/ou funcional e que dá origem à inabilidade de bombear sangue em quantidade suficiente, de forma a preencher as necessidades metabólicas do organismo. No presente trabalho, pretendemos perceber como a interação entre a variação I/D no gene ECA e possíveis moduladores da homeostasia do ferro (Fe) influenciam a IC. Os moduladores em estudo foram: a atividade da redutase da metahemoglobina, o gene Hfe e o gene da heparanase (HPSE) Metodologia: Foi efetuado um estudo de caso-controlo, no qual foram utilizadas 252 amostras de portugueses, 143 indivíduos com IC e 109 controlos saudáveis. Para analisar o polimorfismo no gene HPSE (rs4693608) foi feita a genotipagem por endpoint (LightCycler480). Para analisar os polimorfismos no gene Hfe (H63D e C282Y) recorreu-se à técnica de ARMS Multiplex. Para a análise do polimorfismo no gene ECA (rs4646994 - I/D) realizou-se um PCR. A atividade da redutase da metahemoglobina foi obtida por testes espetrofotométricos. Todos os testes estatísticos necessários foram realizados no software IBM® SPSS® Statistics 26.0, tendo os valores sido considerados significativos para um p < 0,05. Resultados: Verificou-se uma associação entre a IC e: 1) a presença do alelo D do gene HFe (HH vs HD; p=0,049); 2) a presença do alelo A do gene HPSE (AA + GA vs GG; p=0,045; 3) níveis mais baixos da atividade da redutase da metahemoglobina (p=0.019). Verificou-se ainda que as epistasias entre a presença do alelo H ou C do gene Hfe e o alelo D do gene ECA são protetores na IC (p=0,041 para ambas). Conclusão: Os resultados deste estudo evidenciam o papel da homeostasia do ferro e da sua interação com a ECA na IC. O ferro é um componente essencial para o bom funcionamento das mitocôndrias, as quais têm um papel importante no fornecimento de energia ao musculo cardíaco. O conhecimento do perfil genótipo dos doentes em genes moduladores da homeostasia do ferro em interação com o gene ECA, poderá ser uma vantagem na aplicação de uma medicina mais personalizada, permitindo um aconselhamento preventivo e uma terapêutica mais dirigidos.
- Study of the interaction between modulators of iron homeostasis and the ACE gene in heart failurePublication . Gaspar, Marcos A.; Aguiar, Laura; Ferreira, Joana; Faustino, Paula; Mascarenhas, Mário Rui; Menezes Falcão, Luiz; Bicho, Manuel; Inácio, ÂngelaIntroduction: Heart failure (HF) refers to a clinical syndrome composed of a set of symptoms and/or signs that originate from a structural and/or functional cardiac anomaly and that give rise to the inability to pump blood in sufficient quantity, to meet the body's metabolic needs. In the present work, we intend to understand how the interaction between the I/D variation in the ACE gene and possible modulators of iron (Fe) homeostasis influence HF. The modulators under study were: the methemoglobin reductase activity, the Hfe gene and heparanase genes (HPSE) Methodology: A case-control study was carried out with 252 Portuguese people, 143 with HF and 109 healthy controls. To analyze the polymorphism in the HPSE gene (rs4693608) endpoint genotyping (LightCycler480) was performed. To analyze both polymorphisms in the Hfe gene (H63D and C282Y), ARMS Multiplex technique was used. For the analysis of the polymorphism in the ECA gene (rs4646994 - I/D) a regular PCR was performed. Methaemoglobin reductase activity was obtained using spectrophotometric assay. All necessary statistical tests were performed using the IBM® SPSS® Statistics 26.0 software, with values considered significant for p < 0.05. Results: There was an association between HF and: 1) the presence of the D allele of the HFe gene (HH vs HD; p=0.049); 2) the presence of the A allele of the HPSE gene (AA + GA vs GG; p=0.045; 3) lower levels of methemoglobin reductase activity (p=0.019). It was also found that epistasis between the presence of the H or C allele of the Hfe gene and the D allele of the ACE gene are protective in HF (p=0.041 for both). Conclusion: Results of this study highlight the role of iron homeostasis and its interaction with ACE in HF. Iron is an essential component for the proper functioning of mitochondria, which play an important role in providing energy to the heart muscle. Knowledge of the genotype profile of patients, in modulating genes of iron homeostasis in interaction with the ACE gene could be an advantage in the application of a more personalized medicine, allowing preventive counseling and more targeted therapy.